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Appl. cancer res ; 40(4): [1-12], 01 june 2020. ilus, tab
Article in English | LILACS (Americas) | ID: biblio-1103878


Background: Next-generation sequencing (NGS) based assay for finding an actionable driver in non-small-cell lung cancer is a less used modality in clinical practice. With a long list of actionable targets, limited tissue, arduous single-gene assays, the alternative of NGS for broad testing in one experiment looks attractive. We report here our experience with NGS for biomarker testing in hundred advanced lung cancer patients. Methods: Predictive biomarker testing was performed using the Ion AmpliSeq™ Cancer Hotspot Panel V2 (30 tumors) and Oncomine™ Solid Tumor DNA and Oncomine™ Solid Tumor Fusion Transcript kit (70 tumors) on IonTorrent sequencing platform. Results: One-seventeen distinct aberrations were detected across 29 genes in eighty-six tumors. The most commonly mutated genes were TP53 (43% cases), EGFR (23% cases) and KRAS (17% cases). Thirty-four patients presented an actionable genetic variant for which targeted therapy is presently available, and fifty-two cases harbored non-actionable variants with the possibility of recruitment in clinical trials. NGS results were validated by individual tests for detecting EGFR mutation, ALK1 rearrangement, ROS1 fusion, and c-MET amplification. Compared to single test, NGS exhibited good agreement for detecting EGFR mutations and ALK1 fusion (sensitivity- 88.89%, specificity- 100%, Kappa-score 0.92 and sensitivity- 80%, specificity- 100%, Kappa-score 0.88; respectively). Further, the response of patients harboring tyrosine kinase inhibitor (TKI) sensitizing EGFR mutations was assessed. The progression-free-survival of EGFR positive patients on TKI therapy, harboring a concomitant mutation in PIK3CAmTOR and/or RAS-RAF-MAPK pathway gene and/or TP53 gene was inferior to those with sole-sensitizing EGFR mutation (2 months vs. 9.5 months, P = 0.015). Conclusions: This is the first study from South Asia looking into the analytical validity of NGS and describing the mutational landscape of lung cancer patients to study the impact of co-mutations on cancer biology and treatment outcome. Our study demonstrates the clinical utility of NGS testing for identifying actionable variants and making treatment decisions in advanced lung cancer

Humans , Male , Female , Biomarkers, Tumor , High-Throughput Nucleotide Sequencing , Lung Neoplasms , Mutation
Article in English | IMSEAR (South-East Asia), GHL | ID: sea-175498


Background: The urban slums has diversity, but the universal characteristics refer to overcrowding and congestion, lack of hygiene, extremely poor sanitation, lack of garbage disposal facilities, high density of insects and rodents, makes the dwellers more prone to morbidity. Objectives: To study morbidity profile in urban slum dwellers. Methods: Cross sectional study had been carried out between January 2014 to July 2014 on slum dwellers of Udaipur. Information obtained by interviewing the head and/or other family members of about 76 households. Results: The morbidity rate for both sexes was 33.0%. About 31.2% males and 34.6% females were either suffering from or have a history of one or more illness within previous two weeks. Anemia was found in 11.2% of females. Respiratory tract infections and diarrhea were present in 8.8% and 2.1% of studied population respectively. Among five years above age slum dwellers, 18.9%, 38.3% and 31.2% had a habit of smoking, tobacco chewing and alcohol intake respectively. Conclusions: Slum dwellers were unaware of the effective information on hygiene, health and substance use, education, communication activities along with effective health care delivery measures needed.

Article in English | IMSEAR (South-East Asia), GHL | ID: sea-175496


Background: The pre-school age group (2-5 years) was evaluated for nutritional status at Teetardi village near Geetanjali hospital Udaipur. Objectives: To study the nutritional status in pre-school children. Methods: Cross sectional study carried out during February 2014 to June 2014 with 300 children at Teetardi village near Geetanjali hospital Udaipur. Body weight, height recorded with age, gender and also interviewing the mother. Results: The age and sex distribution of 300 children in present study was 52% males and 48% females. The nutritional status in the children was determined as per World Health Organization child growth standards. Result reveals that out of total male children 4.5% were severely stunted and out of total female children 4.2% were severely stunted. Out of total 10.3% of male children and 11.1% of female children were found stunted. Whereas out of total children 3.2% of male children and 4.9% of female children were severely wasted. Out of total children 10.9% of male children and 12.5% of female children were found wasted. Also 7.1% of male children and 5.5% of female children were overweight also found that 1.9% of male children and 0.7% of female children are obese. Conclusions: There is necessity of more education in reference to nutrition and dietary habits including proper antenatal care and postnatal care of mother to reduce the prevalence of nutrition related abnormalities in children.

Indian J Exp Biol ; 2012 Dec; 50(12): 853-861
Article in English | IMSEAR (South-East Asia), GHL | ID: sea-145325


The present study demonstrates that curcumin acts as pro-oxidant and sensitizes human lung adenocarcinoma epithelial cells (A549) to apoptosis via intracellular redox status mediated pathway. Results indicated that curcumin induced cell toxicity (light microscopy and MTT assay) and apoptosis (AnnexinV-FITC/PI labeling and caspase-3 activity) in these cells. These events seem to be mediated through generation of reactive oxygen species (ROS) and superoxide radicals (SOR) and enhanced levels of lipid peroxidation. These changes were accompanied by increase in oxidized glutathione (GSSG), reduced glutathione (GSH) and -glutamylcysteine synthetase (-GCS) activity, but decrease in GSH/GSSG ratio. The induction of apoptosis and decrease in GSH/GSSG ratio was also accompanied by sustained phosphorylation and activation of p38 mitogen activated protein kinase (MAPK). On the other hand, addition of N-acetyl cysteine (NAC), an antioxidant, blocked the curcumin-induced ROS production and rescued malignant cells from curcumin-induced apoptosis through caspase-3 deactivation. However, L-buthionine sulfoximine (BSO), a GSH synthesis blocking agent, further enhanced curcumin-induced ROS production and apoptosis in A549 cells. Decreased GSH/GSSG ratio seems to be a crucial factor for the activation of MAPK signaling cascade by curcumin. The study therefore, provides an insight into the molecular mechanism involved in sensitization of lung adenocarcinoma cells to apoptosis by curcumin.

Article in English | IMSEAR (South-East Asia), GHL | ID: sea-141447


Background and Objective The role of Mycobacterium avium ss paratuberculosis (MAP) in the etiopathology of Crohn’s disease (CD) remains controversial, because of conflicting reports demonstrating the presence of MAP-specific insertion sequence from intestinal biopsy tissues of patients clinically diagnosed for the disease. The present study was carried out to investigate the presence of MAP DNA in the intestinal tissues of CD patients to ascertain the relevance of MAP in Indian patients with CD. Methods Patients diagnosed as CD at our institute were recruited. Healthy individuals without inflammatory bowel disease served as controls. Mucosal biopsy specimens were collected from ileum and colon in duplicates and subjected to histopathological examination and polymerase chain reaction (PCR) amplification. Total DNA (81 CD patients, 85 healthy individuals) and total RNA (12 CD patients, 12 healthy individuals) isolated from tissue specimens was used for amplification of MAP-specific IS900 by nested PCR. Results MAP-specific IS900 DNA and RNA could not be detected by nested PCR in the intestinal tissues of any patient with CD. Conclusion Our results do not support the etiological role of MAP in the pathogenesis of CD in Indian patients.